Nursing(Degree) · First Year · NUR101
Anatomy and Physiology
Anatomy and Physiology is one of the most important foundation courses for nursing students in Zambia. This course helps you understand how the human body is structured and how it functions, from major organs to body systems such as the nervous, cardiovascular, respiratory, and digestive …
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Anatomy and Physiology is one of the most important foundation courses for nursing students in Zambia. This course helps you understand how the human body is structured and how it functions, from major organs to body systems such as the nervous, cardiovascular, respiratory, and digestive systems. A strong grasp of this subject is essential for exams set by nursing schools and regulatory bodies in Zambia. At 25schools, we simplify complex anatomy concepts using exam-focused questions, diagrams, and clear explanations designed for nursing exams. Whether you are preparing for tests, assignments, or final examinations, this course builds the clinical understanding every successful nurse needs. Start studying with 25schools today and gain the confidence to excel in anatomy and physiology exams.
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Hemophagocytic Lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of pathologic immune activation and dysregulation, characterized by uncontrolled hyperinflammation, cytokine storm, and multi-organ failure. For Zambian students, recognition is critical—HLH is frequently FATAL without prompt treatment. It may be PRIMARY (familial, genetic, infancy/early childhood) or SECONDARY (acquired, any age)—associated with infection (EBV, CMV, HIV, TB, malaria, leishmaniasis), malignancy (lymphoma), rheumatologic disease (MAS—macrophage activation syndrome, e.g., AOSD, SLE, JIA). In Zambia: high burden of EBV, HIV, TB, malaria—HLH is underrecognized, underdiagnosed. Pathophysiology: defective perforin/granzyme-mediated cytotoxicity (NK cells, CD8+ T cells) → failure to eliminate antigen-presenting cells → persistent antigen presentation → uncontrolled T-cell, macrophage activation → CYTOKINE STORM (IFN-γ, IL-1, IL-2, IL-6, IL-10, IL-18, TNF-α) → macrophage infiltration, hemophagocytosis, multi-organ dysfunction. Clinical: PERSISTENT HIGH FEVER (>7 days, >38.5°C). HEPATOSPLENOMEGALY. LYMPHADENOPATHY. NEUROLOGIC SYMPTOMS (seizures, altered mental status, irritability, meningismus, cranial nerve palsies, ataxia)—CNS involvement common, poor prognostic sign. RASH. EDEMA. Laboratory: CYTOPENIAS (≥2 lineages: hemoglobin <9 g/dL, platelets <100,000, neutrophils <1,000). HYPERFERRITINEMIA (prominent, often >500 ng/mL, >10,000 ng/mL highly specific). HYPERTRIGLYCERIDEMIA (>265 mg/dL). HYPOFIBRINOGENEMIA (<150 mg/dL) (DIC). Elevated LDH, transaminases, bilirubin. Hyponatremia. LOW/NK CELL ACTIVITY. ELEVATED SOLUBLE CD25 (sIL-2R). TISSUE BIOPSY: hemophagocytosis (bone marrow, lymph node, liver, spleen). Diagnosis: HLH-2004 CRITERIA—molecular diagnosis consistent with HLH OR 5/8 criteria: fever, splenomegaly, cytopenias (≥2 lineages), hypertriglyceridemia/hypofibrinogenemia, hemophagocytosis, low/absent NK activity, hyperferritinemia (>500), elevated sCD25. HScore: weighted probability score (clinical, laboratory)—validated, accessible. Differential: sepsis, severe malaria, typhoid fever, TB, brucellosis, visceral leishmaniasis, lymphoma, leukemia, AOSD, SLE. Management: TREAT UNDERLYING TRIGGER (infection, malignancy). IMMUNOSUPPRESSION: HLH-94/2004 PROTOCOL. DEXAMETHASONE (CNS penetration). ETOPOSIDE (VP-16)—myelosuppressive, anti-cytokine, anti-T cell. CYCLOSPORINE A. INTRATHECAL THERAPY (CNS disease). IVIG. BIOLOGICS: emapalumab (anti-IFN-γ monoclonal antibody—new, expensive), anakinra (IL-1 blockade, MAS). SUPPORTIVE CARE: antimicrobials, transfusions, organ support. HEMATOPOIETIC STEM CELL TRANSPLANTATION (familial, refractory). Prognosis: untreated, universally fatal. With early diagnosis, protocol-driven therapy: survival 50-60%. Poor prognostic factors: CNS involvement, EBV-HLH, delayed diagnosis, refractory disease. Zambian context: HIGH INDEX SUSPICION in patients with persistent fever, cytopenias, splenomegaly, hyperferritinemia. Ferritin widely available. HScore calculator (online, app) feasible. Bone marrow aspiration/biopsy accessible tertiary centres. Etoposide, dexamethasone, cyclosporine available (cancer centres). IVIG limited. Anakinra, emapalumab unavailable. Multidisciplinary approach (paediatrics, medicine, oncology, intensive care). HLH is a MEDICAL EMERGENCY—DO NOT DELAY THERAPY pending confirmatory tests.
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Vasculitis: Overview and Classification
Vasculitis is inflammation of blood vessel walls, leading to stenosis, occlusion, aneurysm formation, hemorrhage, and tissue ischemia. The clinical presentation is determined by the SIZE, TYPE, and LOCATION of affected vessels. For Zambian students, a systematic approach to vasculitis is essential—these are RARE but TREATABLE causes of multi-system disease, frequently misdiagnosed as infection or malignancy. Classification is by vessel size (Chapel Hill Consensus Conference 2012). LARGE VESSEL VASCULITIS: Giant Cell Arteritis (age >50, headache, jaw claudication, vision loss, ↑ESR, temporal artery biopsy, steroid-responsive), Takayasu Arteritis (age <40, female, pulseless, claudication, aortic arch/branch stenosis, hypertension). MEDIUM VESSEL VASCULITIS: Polyarteritis Nodosa (PAN—necrotizing arteritis, renal, visceral aneurysms, mononeuritis multiplex, skin ulcers, NO GLOMERULONEPHRITIS, NO ANCA), Kawasaki Disease (children, fever >5 days, conjunctivitis, oral changes, rash, cervical lymphadenopathy, extremity changes, coronary aneurysms). SMALL VESSEL VASCULITIS: ANCA-ASSOCIATED VASCULITIS (AAV)—Microscopic Polyangiitis (MPA, necrotizing GN, pulmonary capillaritis, p-ANCA/MPO+), Granulomatosis with Polyangiitis (GPA, necrotizing granulomatous inflammation—upper/lower respiratory tract, GN, c-ANCA/PR3+), Eosinophilic Granulomatosis with Polyangiitis (EGPA, asthma, eosinophilia, neuropathy, p-ANCA/MPO+). IMMUNE COMPLEX SMALL VESSEL VASCULITIS: IgA Vasculitis (Henoch-Schönlein purpura—palpable purpura, arthritis, abdominal pain, IgA nephropathy, children > adults), Cryoglobulinemic Vasculitis (HCV, palpable purpura, neuropathy, GN), Anti-GBM Disease (Goodpasture—lung hemorrhage, rapidly progressive GN, anti-GBM). VARIABLE VESSEL: Behçet's Disease (oral/genital ulcers, uveitis, pathergy, thrombosis, arterial aneurysms). SINGLE-ORGAN VASCULITIS: Cutaneous Leukocytoclastic Vasculitis (isolated skin—drugs, infection, idiopathic). VASCULITIS SECONDARY TO: infection (HCV-cryoglobulin, HBV-PAN, HIV, IE), drugs, connective tissue disease (SLE, RA, Sjögren's), malignancy. Diagnostic approach: 1) CONFIRM VASCULITIS (biopsy preferred, angiography for medium/large). 2) CLASSIFY BY VESSEL SIZE (clinical, imaging, pathology). 3) DETERMINE EXTENT (organ involvement). 4) IDENTIFY ETIOLOGY (infection, drug, primary). Laboratory: CBC, creatinine, urinalysis, LFTs, ESR/CRP, ANA, RF, ANCA (MPO, PR3), anti-GBM, cryoglobulins, complement (C3, C4—low in immune complex), HBV/HCV/HIV, blood cultures, echocardiogram. Biopsy: affected tissue (skin, kidney, nerve, artery, lung)—highest diagnostic yield. Angiography: conventional, CT, MR—medium/large vessel (PAN, Takayasu, GCA). Management: STRATIFIED BY SEVERITY, ORGAN THREAT. SEVERE, ORGAN/LIFE-THREATENING: HIGH-DOSE GLUCOCORTICOIDS (prednisone 1 mg/kg/day, IV methylprednisolone) + CYCLOPHOSPHAMIDE (IV pulse or oral) OR RITUXIMAB (AAV). MAINTENANCE (after remission, 3-6 months): low-dose prednisone, azathioprine, methotrexate, rituximab. MILD-MODERATE: glucocorticoids ± methotrexate/azathioprine. SECONDARY VASCULITIS: TREAT UNDERLYING CAUSE (antivirals for HBV/HCV, stop drug, antibiotics for IE). Prognosis: without treatment, mortality high. With early, aggressive immunosuppression, remission achievable (70-90%). Relapse common. Zambian context: VASCULITIS IS UNDERDIAGNOSED. High index suspicion in multi-system disease with fever, constitutional symptoms, organ involvement, elevated acute phase reactants. ANCA testing limited; biopsy essential. Corticosteroids, cyclophosphamide, azathioprine, methotrexate accessible. Rituximab unavailable. Infection screening (TB, HIV, HBV, HCV) mandatory before immunosuppression. Tuberculous vasculitis, HIV-associated vasculitis in differential.
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Granulomatosis with Polyangiitis
Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a necrotizing granulomatous small-vessel vasculitis, strongly associated with c-ANCA/PR3, classically involving upper respiratory tract, lower respiratory tract, and kidneys. For Zambian students, GPA is a diagnostic challenge—it mimics tuberculosis (TB is endemic), leading to misdiagnosis and delayed, potentially fatal treatment. Pathophysiology: necrotizing granulomatous inflammation, vasculitis of small-medium vessels. PR3-ANCA activates neutrophils, endothelial injury. Clinical: UPPER RESPIRATORY (70-100%)—chronic, progressive, destructive: persistent RHINITIS, SINUSITIS, NASAL ULCERS, CRUSTING, EPISTAXIS, SADDLE-NOSE DEFORMITY (nasal cartilage destruction), OTTIS MEDIA, mastoiditis, subglottic stenosis (hoarseness, stridor). LOWER RESPIRATORY (50-90%)—COUGH, HEMOPTYSIS, DYSPNEA, CHEST PAIN. Nodules (multiple, bilateral, cavitating), infiltrates, pleural effusion. Pulmonary capillaritis → diffuse alveolar hemorrhage (life-threatening). RENAL (50-80%)—pauci-immune necrotizing glomerulonephritis (rapidly progressive glomerulonephritis, RPGN). Hematuria (dysmorphic RBCs), RBC casts, proteinuria, hypertension, progressive renal failure (weeks-months). OTHER: OCULAR (50-60%)—scleritis, episcleritis, orbital pseudotumor (proptosis), uveitis. CUTANEOUS (30-50%)—palpable purpura, ulcers, nodules. NEUROLOGIC (20-40%)—mononeuritis multiplex (wrist/foot drop), cranial neuropathy. ARTHRALGIA/MYALGIA (60-70%). Diagnosis: CLINICAL + SEROLOGY + BIOPSY. ANCA: c-ANCA (cytoplasmic) by immunofluorescence; anti-PR3 antibodies (ELISA) positive in 80-90% of active generalized GPA, 50% of limited. p-ANCA/MPO positive in 5-10%. BIOPSY: nasal, sinus, lung, kidney—NECROTIZING GRANULOMATOUS INFLAMMATION + VASCULITIS. Renal biopsy: pauci-immune crescentic GN (no immune complexes on immunofluorescence). LABORATORY: elevated ESR/CRP, normocytic anemia, leukocytosis, thrombocytosis, creatinine elevated, abnormal urinalysis. CHEST IMAGING: nodules (cavitating), infiltrates, alveolar hemorrhage. Management: INDUCTION REMISSION (SEVERE, ORGAN/LIFE-THREATENING: RPGN, pulmonary hemorrhage, cerebral vasculitis). HIGH-DOSE GLUCOCORTICOIDS: IV methylprednisolone 1g x3 days, then prednisone 1 mg/kg/day taper. PLUS CYCLOPHOSPHAMIDE (IV pulse 15 mg/kg q2-3 weeks, or oral 2 mg/kg/day) OR RITUXIMAB (375 mg/m²/week x4). PLASMA EXCHANGE: RPGN with dialysis-dependence, diffuse alveolar hemorrhage, anti-GBM overlap. MAINTENANCE REMISSION (after 3-6 months): azathioprine (2 mg/kg/day) or methotrexate (20-25 mg/week) + low-dose prednisone taper. Rituximab (500 mg q6 months) for refractory, relapsing. DURATION: minimum 18-24 months. LIMITED DISEASE (no renal, no critical organ): methotrexate + glucocorticoids. TRIMETHOPRIM-SULFAMETHOXAZOLE: limited upper respiratory disease, as adjunctive (PJP prophylaxis), may reduce relapse. Prognosis: Without treatment, 1-year mortality 80%. With modern immunosuppression, remission 90%, 5-year survival 75-80%. Relapse rate 30-50% (higher with PR3+, lower with maintenance). Chronic renal impairment common. Zambian context: GPA is a TUBERCULOSIS MIMIC. Pulmonary nodules/cavitation + constitutional symptoms = TB until proven otherwise. However, GPA presents with UPPER RESPIRATORY destructive disease (saddle-nose, nasal crusting, subglottic stenosis) + RENAL involvement (hematuria, RBC casts, rising creatinine). ANCA testing available at University Teaching Hospital, Lusaka. Biopsy essential (nasal, kidney). Cyclophosphamide, corticosteroids, azathioprine, methotrexate accessible. Rituximab unavailable. PJP prophylaxis (TMP-SMX) mandatory. Distinction from TB is critical—misdiagnosis leads to delayed vasculitis therapy (irreversible renal failure, death) OR inappropriate anti-TB therapy (toxicity, no response). High index suspicion in patients with: 1) 'Smear-negative TB' with persistent hematuria/rising creatinine, 2) ENT destructive lesions not responding to standard therapy, 3) Pulmonary-renal syndrome.
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Microscopic Polyangiitis
Microscopic polyangiitis (MPA) is a necrotizing small-vessel vasculitis, strongly associated with p-ANCA/MPO, characterized by pauci-immune necrotizing glomerulonephritis and pulmonary capillaritis, WITHOUT granulomatous inflammation. For Zambian students, MPA is the most common ANCA-associated vasculitis in some populations, and a key cause of rapidly progressive glomerulonephritis (RPGN) and pulmonary-renal syndrome. Pathophysiology: necrotizing vasculitis of small vessels (capillaries, venules, arterioles); pauci-immune (minimal immune complex deposition). MPO-ANCA (p-ANCA) predominant. Clinical: RENAL (90-100%)—pauci-immune necrotizing crescentic GN. Hematuria (dysmorphic RBCs), RBC casts, proteinuria, hypertension, RAPIDLY PROGRESSIVE RENAL FAILURE (weeks). PULMONARY (25-50%)—pulmonary capillaritis → DIFFUSE ALVEOLAR HEMORRHAGE (DAH): dyspnea, cough, hemoptysis, diffuse bilateral alveolar infiltrates, hypoxemia, falling hemoglobin. Pulmonary-renal syndrome = DAH + RPGN. CUTANEOUS (30-60%)—palpable purpura (lower extremities), livedo reticularis, splinter hemorrhages. NEUROLOGIC (20-40%)—mononeuritis multiplex (wrist drop, foot drop), peripheral neuropathy. MUSCULOSKELETAL (50-60%)—arthralgia, myalgia. CONSTITUTIONAL: fever, weight loss, malaise. GPA DISTINCTION: MPA has NO upper respiratory tract granulomatous disease (sinusitis, nasal destruction, saddle-nose, subglottic stenosis); NO nodules/cavities on chest imaging (hemorrhage only). Diagnosis: CLINICAL + SEROLOGY + BIOPSY. ANCA: p-ANCA (perinuclear) by immunofluorescence; anti-MPO antibodies (ELISA) positive in 70-80%. RENAL BIOPSY: pauci-immune crescentic GN—crescents, fibrinoid necrosis, minimal immunoglobulin/complement deposition. LUNG BIOPSY: pulmonary capillaritis—neutrophilic infiltration of alveolar septa, fibrinoid necrosis, hemorrhage. LAB: elevated ESR/CRP, anemia, leukocytosis, thrombocytosis, creatinine elevated, abnormal urinalysis. CHEST IMAGING: diffuse bilateral alveolar infiltrates (DAH), patchy ground-glass. Management: SAME AS GPA. INDUCTION (SEVERE, RPGN, DAH): HIGH-DOSE GLUCOCORTICOIDS (IV methylprednisolone → oral prednisone) + CYCLOPHOSPHAMIDE (IV pulse or oral) OR RITUXIMAB. PLASMA EXCHANGE: RPGN with dialysis-dependence, DAH, anti-GBM overlap. MAINTENANCE: azathioprine or methotrexate + low-dose prednisone. Prognosis: Without treatment, rapidly fatal (renal failure, respiratory failure). With immunosuppression, remission 80-90%, 5-year survival 75%. Relapse rate 30-40% (lower than GPA). Chronic kidney disease common. Zambian context: MPA is an important cause of RPGN and pulmonary-renal syndrome. ANCA testing limited. Renal biopsy essential (accessible tertiary centres). Distinguish from: TB (DAH mimics miliary TB? No), SLE (serology, renal biopsy immunofluorescence—'full-house'), anti-GBM disease (anti-GBM antibodies, linear IgG on renal biopsy). Cyclophosphamide, corticosteroids accessible. Rituximab unavailable. PJP prophylaxis mandatory. High index suspicion: RPGN (rapidly rising creatinine, active urinary sediment) + systemic symptoms + pulmonary hemorrhage = MPA until proven otherwise.
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Eosinophilic Granulomatosis with Polyangiitis
Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is a rare, necrotizing small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophilic tissue infiltration, with or without granulomatous inflammation. For Zambian students, EGPA is a diagnostic challenge—asthma and eosinophilia are common, but EGPA is rare. Recognition of vasculitic phase prevents irreversible organ damage. Pathophysiology: eosinophilic tissue infiltration, necrotizing vasculitis, eosinophilic granulomas. ANCA (p-ANCA/MPO) positive in 30-50% (ANCA+ subset = vasculitic phenotype; ANCA- = eosinophilic tissue phenotype). Three overlapping phases: PRODROMAL (asthma, allergic rhinitis, years), EOSINOPHILIC (peripheral eosinophilia, eosinophilic tissue infiltration—lung, GI, heart), VASCULITIC (life-threatening vasculitis). Clinical: ASTHMA (90-100%)—late-onset, severe, steroid-dependent, precedes vasculitis by 3-9 years. EOSINOPHILIA (>1500/μL, often >10,000). PULMONARY—transient pulmonary infiltrates (eosinophilic pneumonia), nodules, pleural effusion. CARDIAC (40-60%)—LEADING CAUSE OF DEATH. Eosinophilic myocarditis, coronary arteritis, cardiomyopathy, heart failure, arrhythmias, pericarditis, mural thrombus, restrictive cardiomyopathy. NEUROLOGIC (70-80%)—mononeuritis multiplex (wrist/foot drop), peripheral neuropathy. CUTANEOUS (50-70%)—palpable purpura, nodules, livedo, urticaria. RENAL (20-30%)—pauci-immune crescentic GN (ANCA+ subset), mild, less severe than GPA/MPA. GI (30-50%)—abdominal pain, diarrhea, bleeding, perforation (eosinophilic gastroenteritis, vasculitis). ENT—nasal polyps, allergic rhinitis, sinusitis (non-destructive). Diagnosis: CLINICAL + HYPEREOISINOPHILIA + VASCULITIS + BIOPSY. ANCA: p-ANCA/MPO+ in 30-50% (predicts GN, neuropathy, purpura). BIOPSY: necrotizing vasculitis, eosinophilic infiltration, extravascular granulomas (skin, nerve, lung). LAB: eosinophilia, elevated IgE, ESR/CRP, anemia, thrombocytosis, troponin/BNP (cardiac), p-ANCA/MPO. IMAGING: echocardiography (myocarditis, LV dysfunction, mural thrombus), CMR, chest radiograph/CT (infiltrates, nodules). Management: STRATIFIED BY ANCA STATUS, ORGAN INVOLVEMENT, FIVE-FACTOR SCORE (FFS: age >65, cardiac, GI, renal, CNS). HIGH-DOSE GLUCOCORTICOIDS—first-line for all. Prednisone 1 mg/kg/day (or IV methylprednisolone for severe), taper over 12-18 months. ASTHMA: inhaled corticosteroids, bronchodilators. SEVERE, ORGAN-THREATENING (FFS ≥1, ANCA+, cardiac, CNS, renal, severe GI): ADD CYCLOPHOSPHAMIDE (IV pulse or oral) OR RITUXIMAB (ANCA+). MAINTENANCE: azathioprine or methotrexate. REFRACTORY: mepolizumab (anti-IL-5)—FDA-approved for EGPA, steroid-sparing, reduces eosinophils, relapses. Interferon-α. Cardiac: heart failure management, anticoagulation (mural thrombus). Prognosis: With treatment, 5-year survival 80-90%. Mortality: cardiac (50%), renal, CNS. ANCA+ = more vasculitic, renal, neuropathy; ANCA- = more eosinophilic, cardiac. Relapse common (25-50%). Zambian context: EGPA is rare. Distinguish from: TROPICAL PULMONARY EOSINOPHILIA (filariasis, high IgE, asthma, responds to diethylcarbamazine), HYPEREOSINOPHILIC SYNDROME (HES, end-organ damage without vasculitis), chronic eosinophilic leukemia, parasitic infection (strongyloidiasis, hookworm, ascariasis—STOOL EXAMINATION ESSENTIAL), drug reaction (DRESS). Corticosteroids accessible. Cyclophosphamide, azathioprine accessible. Rituximab, mepolizumab unavailable. Cardiac evaluation essential (ECHO).
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IgA Vasculitis
IgA vasculitis (IgAV, formerly Henoch-Schönlein purpura) is the most common childhood vasculitis, characterized by IgA-dominant immune complex deposition in small vessels, manifesting as palpable purpura, arthritis, abdominal pain, and glomerulonephritis. For Zambian students, IgAV is a common differential diagnosis in a child with rash and joint pain; recognition prevents unnecessary investigations and parental anxiety. Pathophysiology: IgA immune complex deposition in vessel walls (skin, GI, kidney, joints) → complement activation → leukocytoclastic vasculitis. Often post-infectious (Group A Streptococcus, viral URI). Clinical: CHILDHOOD (90%, peak 4-6 years), male predominance. ADULTS: more severe renal disease. PALPABLE PURPURA (100%)—the sine qua non. NON-THROMBOCYTOPENIC, symmetric, LOWER EXTREMITIES (buttocks, legs), gravity/pressure-dependent. URTICARIAL, then erythematous macules → palpable purpura, may coalesce, petechiae, ecchymosis. ARTHRITIS (70-80%)—transient, migratory, non-erosive, periarticular swelling, knees, ankles. ABDOMINAL PAIN (50-75%)—colicky, nausea, vomiting, GI BLEEDING (melena, hematochezia), intussusception (ileoileal, 1-5%), perforation (rare). RENAL (20-50%)—IgA NEPHROPATHY (IgAV nephritis). Hematuria (microscopic/gross), proteinuria, hypertension, nephritic syndrome, nephrotic syndrome, RPGN (<5%). SCROTAL: painful testicular swelling (10-15%), mimics torsion. Diagnosis: CLINICAL—palpable purpura + arthritis/arthralgia + abdominal pain + renal involvement. LABORATORY: normal platelet count (ESSENTIAL—exclude thrombocytopenia). Normal/elevated ESR/CRP. Urinalysis: hematuria, proteinuria, RBC casts. SERUM IgA: elevated in 50% (non-specific). NORMAL C3, C4. ANA, ANCA, cryoglobulins NEGATIVE. ASO titre elevated (post-streptococcal). BIOPSY (skin, kidney): leukocytoclastic vasculitis, IgA-dominant immune deposits (direct immunofluorescence). RENAL BIOPSY: IgA nephropathy (mesangial proliferation, IgA deposits). Management: SUPPORTIVE (most cases, self-limited, 4-6 weeks). Analgesia (NSAIDs for arthritis, caution in renal). Hydration. RENAL DISEASE: MILD (isolated hematuria, mild proteinuria)—monitor BP, urinalysis. PERSISTENT PROTEINURIA (>0.5-1g/24h), HYPERTENSION, NEPHRITIC/NEPHROTIC SYNDROME, RPGN—NEPHROLOGY REFERRAL. CORTICOSTEROIDS: not routinely indicated for rash/arthritis/abdo pain (no prevention of nephritis). SEVERE NEPHRITIS: corticosteroids, cyclophosphamide, mycophenolate, azathioprine (evidence limited). RPGN: pulse methylprednisolone, cyclophosphamide. SEVERE GI: corticosteroids (abdominal pain, bleeding, intussusception). Prognosis: EXCELLENT in children. Complete recovery 90%. Renal disease: major determinant of long-term outcome. 1-2% progress to ESRD. Recurrence 30%. Adults: more severe renal disease, poorer prognosis. Zambian context: IgAV is common. Diagnosis is CLINICAL. Palpable purpura + normal platelets = IgAV until proven otherwise. Distinguish from: meningococcemia (septic, ill-toxic), ITP (thrombocytopenia), HSP mimics (SLE, PAN, WG, cryoglobulin). Urinalysis essential for all patients (renal involvement may be silent). No specific treatment; supportive care. Renal monitoring mandatory (BP, urinalysis) for 6-12 months post-resolution. Patient/family education: self-limited, reassurance, recurrence possible.
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Cryoglobulinemic Vasculitis
Cryoglobulinemic vasculitis is a small-vessel vasculitis caused by deposition of cryoglobulins—immunoglobulins that precipitate at cold temperatures and redissolve upon warming—in the walls of capillaries, venules, and arterioles. For Zambian students, this is a critical diagnosis, as the majority (70-90%) of cases are associated with HEPATITIS C VIRUS (HCV) infection, which is prevalent in Zambia. Recognition enables treatment of the underlying viral infection and prevents life-threatening complications (renal failure, neuropathy, gangrene). Classification: TYPE I (10-15%)—monoclonal immunoglobulin (usually IgM) → multiple myeloma, Waldenström's macroglobulinemia, MGUS → hyperviscosity, thrombosis > vasculitis. TYPE II (50-60%)—mixed: monoclonal IgM rheumatoid factor + polyclonal IgG (HCV). TYPE III (30-40%)—mixed: polyclonal IgM rheumatoid factor + polyclonal IgG (HCV, autoimmune disease). Clinical (mixed cryoglobulinemia): MELTZER TRIAD (20-30%)—PURPURA, ARTHRALGIA, FATIGUE. CUTANEOUS (80-90%)—PALPABLE PURPURA (lower extremities, recurrent), ULCERS, LIVEDO RETICULARIS, DIGITAL GANGRENE (cold-precipitation). ARTHRALGIA (70-80%)—non-erosive, symmetric, hands, knees. RENAL (20-60%)—membranoproliferative glomerulonephritis (MPGN) type I. Hypertension, proteinuria, hematuria, nephrotic syndrome, RPGN, progressive renal failure. NEUROLOGIC (40-70%)—peripheral neuropathy (painful, symmetric, sensorimotor), mononeuritis multiplex. COMPLEMENT: LOW C4 (very characteristic), normal C3. HCV INFECTION (70-90%): often chronic, mild LFTs. Other causes: HBV, HIV, connective tissue disease (SLE, Sjögren's). Diagnosis: SERUM CRYOGLOBULINS—detection requires special handling: blood drawn and transported at 37°C, clot at 37°C, serum separated at 37°C, incubated at 4°C for 7 days, cryoprecipitate quantified, typed. LAB: low C4 (90%), rheumatoid factor positive (70-80%), anti-HCV+, HCV RNA+. Urinalysis: proteinuria, hematuria, RBC casts. Renal biopsy: MPGN type I (subendothelial deposits), immunofluorescence: IgM, IgG, C3 (granular). Management: TREAT THE UNDERLYING ETIOLOGY. HCV-ASSOCIATED: DIRECT-ACTING ANTIVIRALS (DAAs)—treatment of choice. Sustained virologic response (SVR) leads to clinical remission in 90% of patients with mild-moderate disease. SEVERE, ORGAN/LIFE-THREATENING (RPGN, mononeuritis multiplex, skin ulcers/gangrene, GI vasculitis): HIGH-DOSE GLUCOCORTICOIDS, CYCLOPHOSPHAMIDE, RITUXIMAB (anti-CD20, B-cell depletion, reduces cryoglobulin production), PLASMA EXCHANGE (rapid removal of cryoglobulins). Rituximab is first-line for severe HCV-cryoglobulinemic vasculitis (with antiviral therapy). NON-INFECTIOUS (idiopathic, CTD): corticosteroids, immunosuppressants, rituximab. Prognosis: HCV-associated—excellent response to DAAs + rituximab in severe. Relapse may occur with viral relapse or reinfection. Renal failure, neuropathy may be irreversible. Zambian context: HIGH HCV PREVALENCE. Consider cryoglobulinemic vasculitis in patient with: palpable purpura + arthralgia + neuropathy + MPGN + low C4 + HCV+. Cryoglobulin testing limited; diagnosis often clinical. DAAs increasingly available (national programme). Rituximab unavailable. Cyclophosphamide, corticosteroids accessible. Plasma exchange limited. Screening for HBV, HIV mandatory.
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Topic 179Coming soon
Anti-GBM Disease
Anti-glomerular basement membrane (anti-GBM) disease is a rare small-vessel vasculitis mediated by autoantibodies directed against the non-collagenous domain of the alpha-3 chain of type IV collagen [α3(IV)NC1], presenting with rapidly progressive glomerulonephritis and/or diffuse alveolar hemorrhage (pulmonary-renal syndrome). For Zambian students, anti-GBM disease is a MEDICAL EMERGENCY—early diagnosis and immediate initiation of immunosuppression + plasma exchange is LIFE-SAVING and RENAL-SAVING. Pathophysiology: anti-GBM antibodies bind to epitopes on α3(IV)NC1 in the GBM and alveolar basement membrane → complement activation, neutrophil recruitment → crescentic GN, pulmonary capillaritis. Associated with HLA-DR15, smoking (pulmonary hemorrhage), hydrocarbon exposure. Concurrent ANCA (double-positive, 20-30%, p-ANCA/MPO). Clinical: RENAL (80-90%)—RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN). Hematuria (dysmorphic RBCs), RBC casts, proteinuria (subnephrotic), oliguria, hypertension, progressive renal failure over days-weeks. PULMONARY (50-80%)—DIFFUSE ALVEOLAR HEMORRHAGE (DAH). Dyspnea, cough, HEMOPTYSIS, diffuse bilateral alveolar infiltrates, hypoxemia, falling hemoglobin. Pulmonary-renal syndrome = DAH + RPGN (60-80%). ISOLATED RENAL (20-40%), ISOLATED PULMONARY (<10%). Diagnosis: SERUM ANTI-GBM ANTIBODIES (ELISA, Western blot)—highly sensitive/specific. ANCA (MPO, PR3) testing mandatory (dual-positivity 20-30%—worse renal outcome). RENAL BIOPSY: crescentic GN (cellular, fibrocellular crescents) in >95%. LINEAR IgG DEPOSITION along GBM (direct immunofluorescence)—PATHOGNOMONIC. LUNG BIOPSY rarely needed. LAB: elevated creatinine, abnormal urinalysis, anemia, normal/low C3/C4. CHEST IMAGING: diffuse bilateral alveolar infiltrates, air bronchograms. Management: URGENT. IMMEDIATE: IV methylprednisolone 500-1000 mg/day x 3-5 days, then oral prednisone 1 mg/kg/day taper. PLUS CYCLOPHOSPHAMIDE (IV or oral, 2 mg/kg/day, adjust renal). PLUS PLASMA EXCHANGE (daily x 14 days, or until anti-GBM antibody negative). RITUXIMAB: alternative to cyclophosphamide (ANCA+). MAINTENANCE: azathioprine or mycophenolate + low-dose prednisone (if dialysis-dependent at presentation and no pulmonary hemorrhage, immunosuppression may be withdrawn after 3-6 months). RENAL REPLACEMENT THERAPY: dialysis, transplantation (delay 6-12 months until anti-GBM negative >6 months). Prognosis: RENAL SURVIVAL determined by CREATININE AT PRESENTATION. Creatinine <5 mg/dL (<440 μmol/L): 80-90% renal survival. Creatinine >5 mg/dL: 30-40% renal survival. OLIGURIA, DIALYSIS-DEPENDENCE at presentation: <10% renal recovery. Pulmonary hemorrhage: excellent response to therapy (90% survival). Without treatment, mortality >90%. Zambian context: ANTI-GBM DISEASE IS ALMOST CERTAINLY UNDERDIAGNOSED. Consider in any patient with: 1) RAPIDLY PROGRESSIVE RENAL FAILURE + active urinary sediment (RBC casts), 2) PULMONARY-RENAL SYNDROME (DAH + RPGN). Anti-GBM antibody testing limited (ELISA). Renal biopsy accessible tertiary centres; linear IgG on immunofluorescence diagnostic. Cyclophosphamide, corticosteroids, azathioprine accessible. Plasma exchange availability limited (Lusaka). High index suspicion, EARLY TRANSFER TO TERTIARY CENTRE for renal biopsy and plasma exchange. Do NOT delay immunosuppression pending transfer. Dialysis may be life-sustaining bridge to recovery or transplantation.
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Coming soon
Topic 180Coming soon
Takayasu Arteritis
Takayasu arteritis (TAK) is a large-vessel vasculitis affecting the aorta and its major branches, predominantly affecting young women (<40 years). For Zambian students, TAK is an important cause of unexplained hypertension, absent pulses, and aortic regurgitation in young adults. Pathophysiology: granulomatous panarteritis of the aorta, aortic arch, and proximal great vessels → intimal hyperplasia, fibrosis, stenosis, occlusion, aneurysm formation. Clinical: THREE PHASES. PRE-PULSELESS (early inflammatory): constitutional symptoms—fever, malaise, weight loss, night sweats, myalgia, arthralgia; carotidynia (painful, tender carotid arteries). PULSELESS (occlusive): vascular insufficiency—absent/diminished pulses (upper extremities > lower), blood pressure discrepancy (>10 mmHg between arms), CLAUDICATION (arm > leg), SYNCOPE (vertebrobasilar), TIA/STROKE (carotid), HYPERTENSION (renal artery stenosis—MOST COMMON CAUSE OF HYPERTENSION IN YOUNG WOMEN WITH TAK), aortic regurgitation (aortic root dilation), heart failure, coronary ostial stenosis (angina, MI). ANEURYSMAL: aortic aneurysm (thoracic, abdominal), rupture. Diagnosis: CLINICAL + IMAGING. No diagnostic antibody. Elevated ESR/CRP (active disease, but may be normal). ANGIography (conventional, CT, MR) is diagnostic—VESSEL STENOSIS, OCCLUSION, DILATATION, COLLATERALS, VESSEL WALL THICKENING/EDEMA (MRI). PET-CT: increased FDG uptake (active inflammation). Classification: Type I (arch branches), Type IIa (ascending aorta, arch, branches), Type IIb (IIa + descending thoracic), Type III (descending thoracic, abdominal), Type IV (abdominal aorta), Type V (combined). Management: CORTICOSTEROIDS—first-line; prednisone 1 mg/kg/day x 1 month, taper over 6-12 months based on clinical, inflammatory response, imaging. STEROID-SPARING: methotrexate, azathioprine, mycophenolate, leflunomide, tocilizumab (IL-6 inhibitor), TNF inhibitors. REVASCULARIZATION: indications—critical stenosis (renal, coronary, cerebral), claudication limiting daily activity, aortic regurgitation, aneurysm >5cm. Bypass grafting (preferred over angioplasty/stenting—restenosis rate high). Timing: AVOID during active inflammation (high restenosis). ANTI-HYPERTENSIVES: control BP (ACE inhibitors for renovascular hypertension). ANTI-PLATELET: aspirin. Prognosis: chronic, relapsing; 5-year survival 80-90%. Morbidity: stroke, blindness, hypertension, heart failure, aneurysm. Zambian context: TAK UNDERDIAGNOSED. Think TAK in YOUNG WOMAN with: 1) HYPERTENSION (especially if refractory, abdominal bruit), 2) ABSENT/DIMINISHED PULSES, BLOOD PRESSURE DIFFERENCE, 3) CLAUDICATION, SYNCOPE, 4) AORTIC REGURGITATION, CAROTIDYNIA. ESR/CRP elevated. CT/MR angiography increasingly accessible (Lusaka). Corticosteroids, methotrexate, azathioprine accessible. Tocilizumab, TNF inhibitors unavailable. Revascularization surgery limited. Hypertension management: calcium channel blockers, ACE inhibitors. Aspirin accessible. High index suspicion.